The performance of viral-mediated gene therapy could be enhanced if there were treatments that had the ability to modulate expression or accessibility of the viral receptors on the cell surface. Such increased expression or accessibility of viral receptors could increase the efficacy of a virus-based therapeutic molecule which, in turn, would allow for a lower burden of gene therapy vector administered to the individual undergoing treatment.
In particular, modulation of the expression or accessibility of coxsackievirus and adenovirus receptors (CAR) is an especially desirable target because most gene therapy technologies rely on adenovirus based systems or any of the Coxsackievirus-based systems being developed. The success of a gene therapy system relies both on the copy number of modified viruses delivered to a single host cell and the number of host cells infected with the modified virus. More copies of the modified viral genomes entering into a host cell allows for higher levels of beneficial gene expression and higher therapeutic protein production to treat the target disease. Similarly, if more host cells take up the therapeutic gene, than the greater treatment/correction of target diseases. Therefore, increasing the amount of viral receptor available on a host cell will increase the number of genetically modified virus that enter a host cell and/or will increase the number of host cells that take up the beneficial virus.
In addition, Coxsackie B viruses, adenoviruses, and Swine Vesicular Disease Virus are serious disease-causing viruses. Currently, no specific therapy exists to treat or lessen the chance of infection from Coxsackie B viruses, adenoviruses, and Swine Vesicular Disease Virus. Supportive care remains the standard treatment. With an ability to modulate the expression or accessibility of CAR, new treatments could be made readily available that protect the host by reducing the amount of viral receptor available on the cell surface thereby (1) decreasing the chance that a virus will enter into a host cell, (2) decreasing the amount of virus entering into a host cell to slow the ability of the virus to take over the cell, (3) allowing the immune system of the host more time to react if a smaller number of viruses do enter the host cell, (4) decreasing viral-induced disease by slowing the time course of infection, (5) blocking or limiting spread of the virus to other cells or organs if an individual is affected or (6) limiting the spread of progeny virus to other individuals in the community by decreasing the number of infectious virions produced.
The current invention shows that certain peptide-based molecules can modulate expression or accessibility of CAR, allowing for better success with gene therapy or treatment of Coxsackie B viruses, adenoviruses, or Swine Vesicular Disease Virus.